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METHOD FOR PRODUCING INTESTINAL ORGANOID DERIVED FROM PLURIPOTENT STEM CELLS

外国特許コード F190009760
整理番号 S2017-0618-C0
掲載日 2019年5月7日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2018JP017572
国際公開番号 WO 2018207714
国際出願日 平成30年5月2日(2018.5.2)
国際公開日 平成30年11月15日(2018.11.15)
優先権データ
  • 特願2017-093418 (2017.5.9) JP
発明の名称 (英語) METHOD FOR PRODUCING INTESTINAL ORGANOID DERIVED FROM PLURIPOTENT STEM CELLS
発明の概要(英語) The present invention addresses the problem of producing a functional intestinal organoid from pluripotent stem cells. An intestinal organoid is produced from pluripotent stem cells through the following steps: (1) a step for differentiating the pluripotent stem cells into endoderm-like cells; (2) a step for differentiating the endoderm-like cells obtained in step (1) into intestinal stem cell-like cells; (3) a step for culturing the intestinal stem cell-like cells obtained in step (2) to form a spheroid; and (4) a step for differentiating the spheroid formed in step (3) to form an intestinal organoid, wherein culturing is carried out in the presence of, in addition to an epidermal growth factor, a BMP inhibitor and a Wnt signal activator, a MEK1/2 inhibitor, a DNA methylation inhibitor, a TGFβ receptor inhibitor and a γ-secretase inhibitor.
従来技術、競合技術の概要(英語) BACKGROUND ART
Small intestine may be orally administered medicament very important to consider the dynamic body is an organ. In non-clinical trials of drugs in human small intestine (absorption, excretion, metabolism) the kinetics of the small intestine for comprehensively evaluating the primary use of epithelial cells is desirable, this is difficult to obtain. In recent years, as new in vitro evaluation system, and intestinal tissue 3 to mimic the three-dimensional tissue structures are of interest (organoids). However, an embryonic stem cell (embryonic stem cells: ES cells) and in the same manner as ES cells of the almost infinite and multipotent has the ability to propagate, the use of drug discovery is also expected to induced pluripotent stem cell (induced pluripotent stem cells: cell iPS) is differentiated from the induced intestinal organoids and prematurely, the pharmacokinetic analysis is not substantially function.
Also, a non-human mammal and disease model is useful in biomedical research. In particular, in the drug discovery laboratory animal and human monkey used as a very similar in many points, the drug-metabolizing enzyme or transporter homology of the amino acid sequence of the 90-95% was observed, similar substrate specificities. Therefore in the non-clinical trials, as well as in vitro in vivo using Cynomolgous is possible to confirm the correlation, to more accurately predict a human can.
ES cells or iPS cells 2 from the three-dimensional (2D) culture produced by the intestinal epithelium cells (for example Patent Document 1, reference 2), and the like using two-dimensional 3 Matrigel (3D) culture produced by organoids in the gastrointestinal tract (for example, Patent Document 3, 4, Non-Patent Document 1-4) are reported.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • NAGOYA CITY UNIVERSITY
  • 発明者(英語)
  • MATSUNAGA Tamihide
  • IWAO Takahiro
  • ONOZATO Daichi
  • OGAWA Isamu
国際特許分類(IPC)
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